ABSTRACT
Asthma has been defined as a disease of chronic airway inflammation in which many cells and cellular products participate with variable degrees of airflow obstruction and hyperresponsiveness that lead to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Prominent among these cellular elements are two cell types referred to as the invariant natural killer T (iNKT) cells and a subpopulation of T cells expressing the molecule CD161, which are both thought to play a role in the pathogenesis of asthma. Although the presence of iNKT and other CD161(+) cells in murine models has been associated with asthma, relatively few studies have been performed in the adult patient with asthma that have been often conflicting and even fewer studies are available in children. The present study was performed to investigate the peripheral blood frequencies of iNKT and CD161(+) T cells in children with asthma. A total of 35 children, 19 stable asthmatic patients, 6 who had experienced an asthmatic attack within 24 hours and had not received any treatment, and 10 healthy controls, aged 6-12 years, were enrolled in the study. iNKT and CD161(+) T-cell frequencies in blood were measured together with quantitative levels of IL-4 and interferon (IFN) γ using a cytofluorimetric approach. The results show that iNKT cells are increased in pediatric asthmatic patients undergoing exacerbations of asthma. These cells also produced less IFN-γ and more IL-4 than children with stable asthma and in healthy control children. These results suggest that iNKT cells might participate in the development of the asthmatic exacerbations. The increased production of IL-4 in conjunction with the decrease of IFN-γ may be mechanistically responsible, at least partially, for the heightening of the immunologic response leading to the asthmatic attack in children. Knowledge of these interactive mechanisms involving the iNKT cell and our understanding of its role in the exacerbation of asthma hold great promise in the development of better diagnostic predictive markers of disease progression as well as new forms of therapeutic interventions.
Subject(s)
Asthma/immunology , Interferon-gamma/metabolism , Interleukin-4/metabolism , Natural Killer T-Cells/immunology , CD4 Antigens/metabolism , Cell Separation , Child , Disease Progression , Female , Flow Cytometry , Humans , Lymphocyte Activation , Lymphocyte Count , Male , NK Cell Lectin-Like Receptor Subfamily B/metabolismABSTRACT
Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.
La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.
Subject(s)
Anti-Asthmatic Agents/administration & dosage , Asthma/drug therapy , Drug Delivery Systems , Administration, Inhalation , Anti-Asthmatic Agents/pharmacokinetics , Humans , Lung/metabolism , Nebulizers and Vaporizers , Tissue DistributionABSTRACT
Resumen La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.
Abstract Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.
Subject(s)
Humans , Asthma/drug therapy , Drug Delivery Systems , Anti-Asthmatic Agents/administration & dosage , Administration, Inhalation , Nebulizers and Vaporizers , Tissue Distribution , Anti-Asthmatic Agents/pharmacokinetics , Lung/metabolismABSTRACT
Allergic bronchopulmonary aspergillosis is a world rare disease with a prevalence between 1 and 2%. It presents in moderate-severe asthma and cistic fibrosis patients. The diagnosis is made in the basis of Rossenberg and Greenberg criteria that can be essential or non essential. We present the case of a 3-year-old boy with allergic bronchopulmonary aspergillosis without bronchiectasies and with a good response to corticosteroids. His mother complained of two years of nasal obstruction, purulent rinorrea, nasal pruritus, sneezing, chronic cough and recurrent wheezing, twice to thrice a month. He also occasionally had vomits and diarrhea in relation with strawberries, banana, cow's milk and chocolate. We made the diagnosis of asthma, allergic rhinitis, sinusitis, and probably food allergy. We treated him with step approach of ICS according to GINA 2006, albuterol PRN, and elimination diet, with bad response. Laboratory exams: Blood white cells with eosinophilia (6%), total serum IgE: 1684 ng/L, aspergillus skin prick test: 4mm, serum IgG-Aspergillus fumigatus: 2.3 mcg/mL, serum IgE-Aspergillus fumigatus: negative, chest roentgenographic parahiliar and apical infiltrates, and chest computed tomography without bronchiectasies. We added prednisone to the treatment for four months, and we observed a very good response; he is now in treatment as mild persistent asthma with ICS low doses. ABPA must be suspected in patients with moderate-severe persistent asthma and a skin prick test positive to Aspergillus fumigatus regardless the age. The treatment with oral corticosteroids is the mainstream of management, and most of the patients have a good response, as we observed with this patient.